DESCRIPTION Spinal cord injury (SCI) often leads to loss of bladder control, resulting in an inability to effectively keep urine in the bladder (incontinence) and an inability to completely empty the bladder when voiding. Incomplete bladder management can lead to infections and even renal failure, in addition to socially awkward situations. Available treatments include undesirable side effects, leaving an unmet need for an alternative therapy utilizing an effective neuroprosthetic device for the SCI population. The objective of this project is twofold: 1) To explore sensory afferent stimulation as a means of restoring bladder function, both continence and micturition, following SCI and 2) To train Dennis Bourbeau to become an leading independent research, restoring function lost to spinal cord injury or other neurological disorders. We propose a translational human study to examine chronic genital nerve stimulation to achieve urinary continence and a preclinical chronic animal study to examine intra-urethral stimulation to achieve micturition. In the human translational study, the clinical effectiveness of genital nerve stimulation (GNS) will be evaluated in veterans with SCI. The hypothesis is that GNS will inhibit bladder hyper-reflexia, which will be manifested in reduced frequency and/or volume of daily urinary incontinence, a decrease in the required frequency of catheterization, an increase in daily urine output and an increased bladder capacity as measured by urodynamics. Surface electrodes will provide the neural interface for GNS, with amplitudes at twice the threshold to evoke the pudendo-anal reflex. During urodynamics testing, bladder pressure and volume expressed will be measured directly and indirectly in response to GNS. These metrics will be observed using an intraurethral catheter to record pressure and to allow for fluid flow, an intrarectal balloon catheter to measure abdominal pressure, and surface electromyogram electrodes to measure pelvic floor activity. With stimulation parameters established, subjects will be sent home with a portable GNS system; they will keep a diary of catheterization and bladder voiding events. This aim will demonstrate the clinical utility of a GNS system by measuring its functional benefits for persons with SCI. These benefits will be related to decreased bladder spasticity, resulting in decreased episodes of incontinence. In the preclinical chronic animal study, a bladder neuroprosthesis will be evaluated. This neuroprosthesis will elicit bladder voiding by targeting sensory afferent fibers arising from the distal urethra in chronically spinalized cats. The hypothesis is that intra-urethral sensory afferent stimulation will produce bladder emptying. We will determine effective stimulation parameters for achieving bladder voiding, then measure voiding volumes in response to intra-urethral sensory nerve stimulation. A comparison between starting volumes and voiding volumes following sensory stimulation will evaluate the performance of the neuroprosthesis to produce micturition. This research is specifically targeted towards the SCI population and will advance an acute model for bladder voiding to a chronic preparation. This work will provide new insights for the development of a sensory afferent stimulation-based neuroprosthetic device to restore bladder function following spinal cord injury. This research is integrated with Dennis Bourbeau's career development plan with the goal of training to become a leading investigator, focusing on rehabilitative therapies for loss of pelvic autonomic functions through sensory stimulation. PUBLIC HEALTH RELEVANCE: The primary goal of this project is to restore bladder function for individuals with spinal cord injury (SCI) or other neurological disorders. Forty percent of people with SCI see restoring their bladder control as the first or second priority (Anderson 2004). For those who have lost full bladder control, standard treatments of care may not completely limit infection risks and have yearly healthcare costs over $20,000 (French, Campbell et al. 2007). This annual cost places a significant burden on each individual's personal finances and the health care system in general. Over 15% of the total U.S. population with SCI are veterans (VA 2009), thus maintaining their bladder care represents a significant load on veteran health care. Providing improved bladder control, as is the ultimate goal of the research proposed here, would enhance the quality of life for veterans with SCI and reduce the financial impact on the Veteran Health Care system.